Niemann-Pick type C (NP-C) is a neurodegenerative lysosomal lipid storage disorder caused by mutations in the NP-C1 or NP-C2 gene. Onset of symptoms can range from infancy until adulthood, and symptoms can be very heterogeneous. In adult-onset NP-C, movement disorders and psychiatric symptoms are frequent (1, 2). Diagnosing NP-C in patients is often challenging and underdiagnosis is likely, particularly in patients with late-onset forms (3). Patients are frequently misdiagnosed with psychiatric disorders, including schizophrenia, atypical psychosis, and mood disorders (4, 5). Moreover, antipsychotic drugs may cause extrapyramidal side-effects more often in patients with NP-C. Otherwise, additional movement disorders caused by NP-C may be wrongly attributed to side-effects of antipsychotic drugs (6).

Early recognition of NP-C is important to provide the right counseling, diagnosis, and treatment. Diagnosing NP-C in an earlier stage will help both the patient and caregivers to better understand the condition, the diversity of (psychiatric) symptoms, and the possible treatments. NP-C disease modifying treatment with miglustat is available and needs to be considered (4–7). From the psychiatric perspective, treatment of psychiatric symptoms in patients with NP-C may differ from other psychiatric conditions. For example, use of typical antipsychotics in patients with NP-C needs to be avoided as these are more likely to cause extrapyramidal side-effects (6). Also, psychosis in these patients may appear treatment resistant, and antipsychotic drugs may cause paradoxical worsening (7, 8).

In general, electroconvulsive therapy (ECT) is effective and–therefore–a good alternative for patients suffering severe treatment-resistant psychosis, depression, catatonia, and delirium (9). ECT is safely performed under general anesthesia and with muscle relaxation. Using an electrical stimulus, neuronal functioning of the brain is altered. This elicits brief seizure activity which propagates throughout the brain and terminates by itself due to several inhibitory processes (10). In patients with NP-C, data about the effectiveness of ECT is limited. Also, the influence of abnormal lysosomal lipid storage, as in NP-C, on seizure initiation, propagation, and termination is unknown.

Here, we describe an adolescent male with NP-C who presented with catatonia and was successfully treated with ECT.

A 23-year-old male patient was referred to our center because of a second episode of catatonia. He had a medical history of major depressive disorder, delusions and catatonia when he was 16 years-of-age, but the patient was healthy otherwise. He was a successful secondary school pupil, loved playing piano, and worked as a volunteer. There was no family history of psychiatric disorders and no consanguinity. A psychologist estimated his intellect to be normal, with verbal and motor performance in the average range and the processing speed below average. During the first episode, the patients showed psychotic and catatonic symptoms. Underlying physical conditions were excluded by normal results of general laboratory and cerebral spinal fluid examinations (especially focusing on infections and paraneoplastic disorders), computed tomography (CT) and magnetic resonance image (MRI) of the brain. Treatment of the catatonic features with lorazepam was started (maximum 24 mg/24 h) without any improvement, and even showed a paradoxical worsening effect with disappearance of speed and functional physical activity. Subsequently, a course of ECT was initiated twice a week [bifrontotemporal (BL) electrode placement; initial seizure threshold (IST) 25.2 mC; electrical dose ranged: 50.4–151.1 mC, pulse width 0.5 ms, motor seizure duration ranged: 15–96 s, electroencephalography (EEG) seizure duration range: 22–257 s; device: Thymatron IV (Somatics Incorporation, Lake Bluff, Illinois, USA)], leading to prompt recovery after four ECT-sessions. ECT was then discontinued, against the ECT guideline. However, after eight days the patient showed a relapse of symptoms. Twenty-one more ECT-sessions followed, leading to complete remission of symptoms. Since bipolar disorder was among the working hypotheses, aripiprazole 30 mg was given as maintenance therapy. However, this was tapered off to stop after six months due to extrapyramidal side-effects.

After this ECT-course, the patient mentioned that he was no longer able to play piano, because he could not switch between the keys and the sheet music. Neurological examination revealed an inability to look up and in particular down, compatible with a vertical supranuclear gaze palsy (VSGP). Also, splenomegaly, subtle dystonia and parkinsonism were observed. This combination of psychiatric symptoms, movement disorders, and VSGP raised the suspicion of an underlying inborn error of metabolism. A diagnosis of NP-C was genetically confirmed [compound heterozygous mutations c.346C>T (p.R116X) and c.247A>G in the NP-C1 gene]. Treatment with miglustat was initiated. After 14 months his treatment was terminated because of side-effects including headaches, lack of energy, cognitive impairment, and depressive mood. In the following weeks, after discontinuation of miglustat, his condition improved. After the discontinuation of the pharmacological therapy, the patient continued his homeopathic medicines, which he and his parents believe contributed to his improvement.

At 23 years of age he presented with a recurrence of catatonia. At admission, clouded consciousness, mutism, grimacing, stereotypy, mannerisms, negativism, excitement and perseveration were seen. He was rated with a severity score of 36 (out of 69) on the Bush-Francis Catatonia Rating Scale (BFCRS) (11). Laboratory examination, including whole blood count, electrolytes, renal function, vitamins, CRP, and liver panel showed no abnormalities. The lipid panel showed no abnormalities either, apart a low HDL 0.74 mmol/L (laboratory reference: >1.00 mmol). The cytochrome P450 genotyping showed increased CYP2D6 activity. MRI of the brain appeared normal. Treatment with oral lorazepam (maximum 7.5 mg/24 h) failed again and even showed a paradoxical worsening effect with psychotic features, disinhibition, and excitement. ECT was started with BL electrode placement, using a constant-current (0.9 ampère), brief-pulse (1.0 ms) device (Thymatron IV; Somatics Incorporation, Lake Bluff, Illinois, USA), with the first treatment dose at 75.6 mC based on his IST at the first ECT-course. Directly after the first ECT-session, improvement of the level of consciousness, mobility, and verbal responsiveness was observed and his condition progressed to full recovery after 11 BL ECT-sessions (ECT-doses ranged: 75.6–453.6 mC; pulse width 1.0 ms; motor seizure duration ranged: 49–85 s, EEG seizure duration ranged: 97–180 s). Remarkably, during this ECT-course the threshold for inducing seizures increased rapidly. After four ECT-sessions, a charge of 453.6 mC was needed to induce a seizure. After the ECT-course, the BFCRS score was rated zero. He was able to read, solve puzzles, and eventually ride his bicycle again. In accordance with the patient and his parents, no psychopharmacological maintenance treatment was prescribed because he had previously experienced severe side-effects. However, he continued the homeopathic medicines. One year later, his condition is still improving.

We present a case of a young patient showing recurrent catatonia, which was treated successfully with ECT repeatedly. In this exemplary ECT-patient, NP-C was diagnosed not until after the first ECT-course when initial psychopharmacologic treatment for catatonia had failed, and antipsychotics and benzodiazepines showed significant side-effects. Clinicians should be aware of NP-C in patients referred for ECT, especially in the case of treatment resistance, neurological symptoms (e.g., extrapyramidal signs), and intolerance of psychopharmacological drugs. During the ECT-course seizure threshold in this patient increased substantially, leading to questions about the influence of NP-C on neuroexcitability.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.